HDV Flashcards
What tests are performed during HDV screening test?
IgM
IgG
If IgM/IgG pos - for HDV RNA PCR
Chronic HBV, now has inflammation of liver
HBV DNA viral load not detectable
How might this be explained?
HDV is dominant virus - hijacks cell. It does not encode its own envelope proteins, so dependent of HBsAg in same cell to complete its life cycle
If we test for HDV, will find high level of RNA
What group do they belong to in Baltimore classification of viruses
HDV
HBV
HDV - Group 5 -ssRNA virus
HBV - Group 7 - retroviruses
HDV virus genome does not encode its own envelope proteins or replication proteins
What enzyme helps with replication?
replication is mediated by the host cell DNA-dependent RNA polymerase
How many people with HBV are co-infected with HDV?
5-10%
What is risk of HBV/ HDV co-infection?
Higher risk of cirrhosis/ HCC, and this occurs much earlier
e.g cirrhosis and liver failure in 10 years
What is best way to prevent HDV infection?
Screen for HBV infection
Immunise against HBV
Patient with HBV/ HDV co-infection
Who should we treat?
If anti-HDV pos, but HDV RNA neg - do have have current HDV infection, so do not need treatment
All patients with co-infection should be treated, given risk of progression.
Risk stratify by looking at HBV markers, ALT, fibro scan, liver biopsy
Patient with HBV/ HDV co-infection
When should treatment be given for HBV?
HBV treatment is not active against HDV.
But if we can clear HBV, good chance of clearing HDV
Two approaches:
1. General summary - start tenofovir/ entecavir on all patients who are HBV DNA and HDV RNA positive
- EASL
- start tenofovir/ entecavir on all patients who have persistent HBV viral load >2000 iu/ml
- tenofovir/ entecavir might be considered in advanced liver disease
- tenofovir/ entecavir should be considered in all patients with decompensated cirrhosis, and detectable HBV DNA
Patient with HBV/ HDV co-infection
All patients with HDV should be treated
What are drug options for HDV?
PegIFN-alpha
Bulevirtide
Lonafarnib (in research)
Inhibitors of HBsAg release - in development
Liver transplant if liver failure
HDV drug options
What are their mechanisms of action?
PegIFN-alpha
Bulevirtide
Lonafarnib
PegIFN-alpha - immunomodulator. Upregulate host response, to help natural immunity clear virus
Bulevirtide - NTCP entry inhibitor. Prevents HDV from binding to new hepatolocytes
Lonafarnib - prenylation inhibitor. Prevents HDV antigen protein assembly
Prenylation - addition of hydrophobic molecule to a protein
What are drug side effects of bulevirtide?
bile acid increases - unclear significance
mild pruritis
injection site reactions - once weekly injection
HBV/ HDV patient commenced on bulevirtide
What monitoring is required?
HDV RNA and ALT every 4 weeks
if stable, monitor at longer intervals
safety and tolerability e.g injection site reactions
What are the NICE recommendations for use of bulevritide?
Bulevirtide is recommended as an option for treating chronic hepatitis D in adults with compensated liver disease only if:
There is evidence of significant fibrosis (METAVIR stage F2 or above or Ishak stage 3 or above) and
their hepatitis has not responded to peginterferon alfa‑2a (PEG‑IFN) or they cannot have interferon-based therapy.
Patient must have failed PEG-IFN before being offered bulevirtide treatment
HBV and HDV can have a co-infection or super infection
What is the difference?
Co-infection - infected at same time. Usually normal clinical course with acute hepatitis episode
Super-infection - chronic HBV infection, who develops a new HDV infection. Higher risk of acute hepatitis and rapid progression
